Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage
Da-Qiang Ke
Zhi-Yang Chen
Zhou-Ling Li
Xia Huang
Hui Liang
1.Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China2.Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China3.Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China4.Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China5.Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
摘要：Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elu-sive. The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH. The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms. In this study, a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats. Z-IETD-FMK (0.5, 1, 2 mg/kg; an inhibitor of caspase-8) was delivered via intravenous (tail vein) injection immediately after subarachnoid hemorrhage. After 12 hours of subarachnoid hemorrhage, western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours, peaked at 24 hours, and then decreased at 72 hours after subarachnoid hem-orrhage. Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage. Z-IETD-FMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage. The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coor-dination at 21-27 days after subarachnoid hemorrhage. Furthermore, inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3, caspase-1, and interleukin-1β after subarachnoid hemorrhage. In conclusion, our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation. The study was approved by the In-stitutional Animal Ethics Committee of the First Affiliated Hospital, School of Medicine, Zhejiang University, China (approval No. 2016-193) on February 25, 2016.
机标关键词：
分类号：R453(治疗学)R741(神经病学)R743.34(神经病学与精神病学)
论文发表日期：2020-07-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 1283-1289 )
英文信息